Mitofusin 2 in macrophages links mitochondrial ROS production, cytokine release, phagocytosis, autophagy, and bactericidal activity

Mitofusin 2 (Mfn2) plays a major role in mitochondrial fusion and in the maintenance of mitochondria-endoplasmic reticulum contact sites. Given that macrophages play a major role in inflammation, we studied the contribution of Mfn2 to the activity of these cells. Pro-inflammatory stimuli such as lipopolysaccharide (LPS) induced Mfn2 expression. The use of the Mfn2 and Mfn1 myeloid-conditional knockout (KO) mouse models reveals that Mfn2 but not Mfn1 is required for the adaptation of mitochondrial respiration to stress conditions and for the production of reactive oxygen species (ROS) upon pro-inflammatory activation. Mfn2 deficiency specifically impairs the production of pro-inflammatory cytokines and nitric oxide. In addition, the lack of Mfn2 but not Mfn1 is associated with dysfunctional autophagy, apoptosis, phagocytosis, and antigen processing. Mfn2floxed;CreLysM mice fail to be protected from Listeria, Mycobacterium tuberculosis, or LPS endotoxemia. These results reveal an unexpected contribution of Mfn2 to ROS production and inflammation in macrophages

Urotensinergic system genes in experimental subarachnoid hemorrhage

[ES] Objetivo: El vasoespasmo cerebral, una de las principales complicaciones secundarias a hemorragia subaracnoidea (HSA), se caracteriza por una constricción arterial que tiene lugar principalmente entre el día 4 y la segunda semana. La urotensina-II (U-II) ha sido definida como el péptido con mayor capacidad vasoconstrictora en mamíferos. Quisimos analizar los niveles séricos de U-II, así como los niveles de expresión de los genes de U-II, péptido relacionado con urotensina y receptor de urotensina, en un modelo murino experimental de HSA.Diseño: Estudio experimental.Ámbito: Quirófano experimental del Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío.Participantes: Noventa y seis ratas Wistar: 74 con inyección percutánea de sangre (HSA), 22 con inyección percutánea de 100 μL de salino (Sham).Intervenciones: Día 1: extracción de muestras de sangre. Posteriormente, inyección percutánea de 100 μL de salino (Sham) o de sangre (HSA) en el espacio subaracnoideo. Día 5: extracción de muestras de sangre y sacrificio del animal.Principales variables de interés: Peso, mortalidad precoz, niveles séricos de U-II, valores de ARNm de U-II, péptido relacionado con urotensina y receptor de urotensina.Resultados: Observamos un incremento en los niveles de U-II sérica en el grupo HSA desde el día 1 (0,62 pg/mL [RI 0,36-1,08]) al día 5 (0,74 pg/mL [RI 0,39-1,43]) (p < 0,05); pero no observamos tal diferencia en el grupo Sham (0,56 pg/mL [RI 0,06-0,83] día 1; 0,37 pg/mL [RI 0,23-0,62] día 5) (p = 0,959). Se encontraron diferencias en los niveles de U-II entre ambos grupos al quinto día (p < 0,05). El análisis de curvas ROC demostró que la U-II sérica al quinto día (AUC = 0,691), ARNm de péptido relacionado con urotensina (AUC = 0,706) y ARNm de receptor de urotensina (AUC = 0,713) podían discriminar entre ratas Sham y HSA. Además, definimos un rango de normalidad para los niveles de U-II séricos en ratas: 0,56 pg/mL (RI 0,06-0,83).Conclusión: Este estudio demuestra por primera vez que el sistema urotensinérgico ve incrementada su expresión en el quinto día en un modelo de HSA.[EN] Objective: Cerebral vasospasm, one of the main complications of subarachnoid hemorrhage (SAH), is characterized by arterial constriction and mainly occurs from day 4 until the second week after the event. Urotensin-II (U-II) has been described as the most potent vasoconstrictor peptide in mammals. An analysis is made of the serum U-II concentrations and mRNA expression levels of U-II, urotensin related peptide (URP) and urotensin receptor (UT) genes in an experimental murine model of SAH.Design: An experimental study was carried out.Setting: Experimental operating room of the Biomedicine Institute of Seville (IBiS), Virgen del Rocío University Hospital (Seville, Spain).Participants: 96 Wistar rats: 74 SAH and 22 sham intervention animals.Interventions: Day 1: blood sampling, followed by the percutaneous injection of 100 μl saline (sham) or blood (SAH) into the subarachnoid space. Day 5: blood sampling, followed by sacrifice of the animals.Main variables of interest: Weight, early mortality, serum U-II levels, mRNA values for U-II, URP and UT.Results: Serum U-II levels increased in the SAH group from day 1 (0.62 pg/mL [IQR 0.36–1.08]) to day 5 (0.74 pg/mL [IQR 0.39–1.43]) (p < 0.05), though not in the sham group (0.56 pg/mL [IQR 0.06–0.83] day 1; 0.37 pg/mL [IQR 0.23–0.62] day 5; p = 0.959). Between-group differences were found on day 5 (p < 0.05). The ROC analysis showed that the day 5 serum U-II levels (AUC = 0.691), URP mRNA (AUC = 0.706) and UT mRNA (AUC = 0.713) could discriminate between sham and SAH rats. The normal serum U-II concentration range in rats was 0.56 pg/mL (IQR 0.06–0.83).Conclusion: The urotensinergic system is upregulated on day 5 in an experimental model of SAH.Peer reviewe

El copyright en cuestión. Diálogos sobre propiedad intelectual

Análisis desde un enfoque editorial y legal del debate sobre la propiedad intelectual y sus formas en el contexto digital. Un debate que interesa a profesores, estudiantes, editores, divulgadores, bibliotecarios y autores. En el libro se estudia los derechos de autor y las cuestiones relacionadas con la propiedad intelectual provocadas por el impacto de la tecnología en la edición, creación, docencia e investigación al tiempo que se ofrece propuestas de futuro para conciliar los puestos de vista de autores, universidades, lectores, editoriales y bibliotecas.In the book analysis and debate, from an editorial and legal approach, intellectual property and its forms in the digital environment is made. A debate that concerns teachers, students, publishers, disseminators, librarians and authors. In the book copyright issues and intellectual property caused by the impact of technology in the editing, creating, teaching and research is studied. Finally, proposals for the future are offered to reconcile the positions of view of authors, universities, readers, publishers and libraries

Monocyte Phenotype and Polyfunctionality Are Associated With Elevated Soluble Inflammatory Markers, Cytomegalovirus Infection, and Functional and Cognitive Decline in Elderly Adults.

Monocytes are mediators of the inflammatory response and include three subsets: classical, intermediate, and nonclassical. Little is known about the phenotypical and functional age-related changes in monocytes and their association with soluble inflammatory biomarkers, cytomegalovirus infection, and functional and mental decline. We assayed the activation ex vivo and the responsiveness to TLR2 and TLR4 agonists in vitro in the three subsets and assessed the intracellular production of IL1-alpha (α), IL1-beta (β), IL-6, IL-8, TNF-α, and IL-10 of elderly adults (median 83 [67-90] years old;n= 20) compared with young controls (median 35 [27-40] years old;n= 20). Ex vivo, the elderly adults showed a higher percentage of classical monocytes that expressed intracellular IL1-α (p= .001), IL1-β (p= .001), IL-6 (p= .002), and IL-8 (p= .007). Similar results were obtained both for the intermediate and nonclassical subsets and in vitro. Polyfunctionality was higher in the elderly adults. The functionality ex vivo was strongly associated with soluble inflammatory markers. The activation phenotype was independently associated with the anti-cytomegalovirus IgG levels and with functional and cognitive decline. These data demonstrate that monocytes are key cell candidates for the source of the high soluble inflammatory levels. Our findings suggest that cytomegalovirus infection might be a driving force in the activation of monocytes and is associated with the functional and cognitive decline

The age again in the eye of the COVID-19 storm: evidence-based decision making.

One hundred fifty million contagions, more than 3 million deaths and little more than 1 year of COVID-19 have changed our lives and our health management systems forever. Ageing is known to be one of the significant determinants for COVID-19 severity. Two main reasons underlie this: immunosenescence and age correlation with main COVID-19 comorbidities such as hypertension or dyslipidaemia. This study has two aims. The first is to obtain cut-off points for laboratory parameters that can help us in clinical decision-making. The second one is to analyse the effect of pandemic lockdown on epidemiological, clinical, and laboratory parameters concerning the severity of the COVID-19. For these purposes, 257 of SARSCoV2 inpatients during pandemic confinement were included in this study. Moreover, 584 case records from a previously analysed series, were compared with the present study data. Concerning the characteristics of lockdown series, mild cases accounted for 14.4, 54.1% were moderate and 31.5%, severe. There were 32.5% of home contagions, 26.3% community transmissions, 22.5% nursing home contagions, and 8.8% corresponding to frontline worker contagions regarding epidemiological features. Age > 60 and male sex are hereby confirmed as severity determinants. Equally, higher severity was significantly associated with higher IL6, CRP, ferritin, LDH, and leukocyte counts, and a lower percentage of lymphocyte, CD4 and CD8 count. Comparing this cohort with a previous 584-cases series, mild cases were less than those analysed in the first moment of the pandemic and dyslipidaemia became more frequent than before. IL-6, CRP and LDH values above 69 pg/mL, 97 mg/L and 328 U/L respectively, as well as a CD4 T-cell count below 535 cells/μL, were the best cut-offs predicting severity since these parameters offered reliable areas under the curve. Age and sex together with selected laboratory parameters on admission can help us predict COVID-19 severity and, therefore, make clinical and resource management decisions. Demographic features associated with lockdown might affect the homogeneity of the data and the robustness of the results

El Quijote a través de la Educación Física : propuestas prácticas para Educación Infantil, Primaria, Secundaria y Bachillerato

Resumen basado en el de la publicaciónSe muestra el procedimiento seguido para trabajar la obra de Miguel de Cervantes, El Ingenioso hidalgo Don Quijote de la Mancha, desde el área de Educación Física, a través de los juegos populares que aparecen en ella. Se presenta el relato de la investigación llevada a cabo, así como su adaptación y aplicación en Educación Física en las etapas de Educación Infantil, Primaria, Secundaria y Bachillerato. A partir de la localización y el conocimiento de los juegos motores populares que aparecen en la novela, se pasa al plan de acción: diseñar una propuesta de intervención educativa en las distintas etapas o niveles mencionados. A estos efectos, el juego como elemento cultural se ha trabajado en la pista-gimnasio a partir de los textos del Quijote, de su lectura y comentario en el aula desde la perspectiva globalizadora en Infantil, en las áreas de Lengua, Música y Conocimiento del Medio en Primaria y en las áreas de Lengua, Ciencias, Historia, Música y Geografía en Educación Secundaria y Bachillerato, todo ello complementándose con la realización de clases teórico-prácticas en la pista y en el gimnasio en las clases de Educación Física.AndalucíaBiblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín 5 -3 Planta; 28014 Madrid; Tel. +34917748000; [email protected]

La creación de un aula práctica para la enseñanza jurídica

El presente proyecto de innovación docente tiene como objetivo la creación de un aula práctica para el acompañamiento de las explicaciones de cátedra mediante la publicación en acceso abierto y gratuito de los casos prácticos elaborados sobre resoluciones judiciales y administrativas a lo largo del curso académico.Depto. de Derecho CivilDepto. de Derecho Mercantil, Financiero y TributarioFac. de DerechoFac. de Trabajo SocialFALSEsubmitte